title: JAM-A regulates epithelial proliferation through Akt/β-catenin signalling.
abstract: Expression of the tight junction protein junctional adhesion molecule-A (JAM-A) has been linked to proliferation and tumour progression. However, a direct role for JAM-A in regulating proliferative processes has not been shown. By using complementary in vivo and in vitro approaches, we demonstrate that JAM-A restricts intestinal epithelial cell (IEC) proliferation in a dimerization-dependent manner, by inhibiting Akt-dependent β-catenin activation. Furthermore, IECs from transgenic JAM-A(-/-)/β-catenin/T-cell factor reporter mice showed enhanced β-catenin-dependent transcription. Finally, inhibition of Akt reversed colonic crypt hyperproliferation in JAM-A-deficient mice. These data establish a new link between JAM-A and IEC homeostasis.
authors.affiliation: Epithelial Pathobiology Research Unit, Department of Pathology, Emory University, Whitehead Biomedical Research Building, Room 105E, 615 Michael Street, Atlanta, Georgia 30322, USA.
authors.forename: Porfirio
authors.initials: P
authors.lastname: Nava
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Capaldo
authors.forename: Stefan
authors.initials: S
authors.lastname: Koch
authors.forename: Keli
authors.initials: K
authors.lastname: Kolegraff
authors.forename: Carl Robert
authors.initials: CR
authors.lastname: Rankin
authors.forename: Attila E
authors.initials: AE
authors.lastname: Farkas
authors.forename: Mattie E
authors.initials: ME
authors.lastname: Feasel
authors.forename: Linheng
authors.initials: L
authors.lastname: Li
authors.forename: Caroline
authors.initials: C
authors.lastname: Addis
authors.forename: Charles A
authors.initials: CA
authors.lastname: Parkos
authors.forename: Asma
authors.initials: A
authors.lastname: Nusrat
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D008817:Mice, Mutant Strains; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D012263:Ribonucleosides / Q000494:pharmacology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D019108:Tight Junctions / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; C498686:F11r protein, mouse; D011956:Receptors, Cell Surface; D012263:Ribonucleosides; D051176:beta Catenin; C023764:triciribine; D051057:Proto-Oncogene Proteins c-akt